ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.235G>A (p.Ala79Thr) (rs202004587)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 15
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
AlTemaimi Lab, Faculty of Medicine,Kuwait University RCV000409443 SCV000577862 pathogenic Cowden syndrome 1 2017-05-19 no assertion criteria provided clinical testing CMT panel and gene duplication assays were negative and investigative exome sequencing was conducted. Clinical presentation is 80% match with Cowden Syndrome (exception unilateral pes cavus).
Ambry Genetics RCV000129085 SCV000183790 likely benign Hereditary cancer-predisposing syndrome 2018-01-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other data supporting benign classification
Biesecker Lab/Human Development Section,National Institutes of Health RCV000034594 SCV000043462 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
ClinGen PTEN Variant Curation Expert Panel RCV000123046 SCV000840467 likely benign PTEN hamartoma tumor syndrome 2018-04-06 reviewed by expert panel curation PTEN c.235G>A (p.A79T) meets criteria to be classified as likely benign for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (Mester et al. 2018; manuscript in preparation). Please see a summary of the rules and criteria codes in the 'PTEN ACMG Specifications Summary' document (assertion method column). BS1: Allele frequency of 0.0045 (0.45%, 9/1984 alleles) in the GME variome. (PMID 27428751) BS2_P: Meets criteria for BS2 (observed in the homozygous state in at least one healthy or PHTS-unaffected individual) but BS1 is also applied. (Internal laboratory contributor(s) SCV000222198.12) PP2: PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.
Color RCV000129085 SCV000902713 likely benign Hereditary cancer-predisposing syndrome 2016-04-11 criteria provided, single submitter clinical testing
Counsyl RCV000409443 SCV000487786 uncertain significance Cowden syndrome 1 2015-11-17 criteria provided, single submitter clinical testing
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000123046 SCV000257666 uncertain significance PTEN hamartoma tumor syndrome 2015-07-10 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000515193 SCV000611427 uncertain significance Endometrial carcinoma; Macrocephaly/autism syndrome; Meningioma, familial; Squamous cell carcinoma of the head and neck; Bannayan-Riley-Ruvalcaba syndrome; Malignant tumor of prostate; Follicular thyroid carcinoma; VACTERL association with hydrocephalus; Glioma susceptibility 2; Cowden syndrome 1; Cutaneous malignant melanoma 1 2017-05-23 criteria provided, single submitter clinical testing
GeneDx RCV000034594 SCV000222198 likely benign not provided 2018-07-18 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
GeneKor MSA RCV000129085 SCV000822140 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000626250 SCV000746903 uncertain significance Macrocephaly/autism syndrome 2017-12-18 criteria provided, single submitter clinical testing
Invitae RCV000123046 SCV000166341 uncertain significance PTEN hamartoma tumor syndrome 2018-06-29 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 79 of the PTEN protein (p.Ala79Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs202004587, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in the literature in individuals with PTEN hamartoma tumor syndrome (PHTS) (PMID: 21659347, 21956414, 21194675, 21343951), and a personal and family history of breast cancer (PMID: 12372056, 29371908). It has also been observed in unaffected individuals (PMID: 22703879). This variant is also known as 1269G>A, A78T, and A75T in the literature. ClinVar contains an entry for this variant (Variation ID: 41682). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Mendelics RCV000123046 SCV000838417 uncertain significance PTEN hamartoma tumor syndrome 2018-07-02 criteria provided, single submitter clinical testing
PreventionGenetics RCV000034594 SCV000806056 uncertain significance not provided 2014-09-18 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000034594 SCV000888591 uncertain significance not provided 2018-01-18 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.